Delta2-1,3,4-oxadiazoline-4-carbonitriles and the preparation thereof



United States Patent 3,509,169 A -1,3,4-OXADIAZOLINE-4-CARBONITRILES ANDTHE PREPARATION THEREOF Frank Dennis Marsh, Wilmington, Del., assignorto E. I.

du Pont de Nemours and Company, Wilmington, Del., a corporation ofDelaware No Drawing. Filed June 5, 1967, Ser. No. 643,350 Int. Cl. C07d85/54 US. Cl. 260307 10 Claims ABSTRACT OF THE DISCLOSURE A 1,3,4oxadiazoline 4 carbonitriles having selected fluorinated substituents inthe positions formed by the reaction of a mixture of a fluoro-aliphaticketone, cyanogen azide and an aliphatic nitrile or cyanogen halide at atemperature of 25-125 C. are claimed. These compounds are useful as soilfungicides.

BACKGROUND OF THE INVENTION Field of the invention This inventionrelates to fluorine-containing carbonitrile heterocyclic compounds andto the process for their preparation.

Description of the prior art Heterocyclic compound-s have long beenknown to have valuable biological activity making many of them usefulfor a variety of physiological and biological applications. Theincorporation of fluorine into organic compounds has been shown toimpart valuable properties into the fluoroorgam'c compounds and in somecases, the compounds have vastly diflerent solubility and stabilityproperties.

It is desirable to incorporate fluorine into heterocyclic compoundssince improved and, in some cases, totally new biologically activecompounds result.

Some A -oxadiazoline compounds are known in the chemical literature. Forexample, Huisgen et. al., J. Org. Chem., 24, 892 (1959) (cf. also Proc.Chem. Soc., 357 (1961)) reports that 2,4,5-triphenyl-A-1,3,4-oxadiazoline was formed by the thermolysis of2,5-diphenyltetrazole in the presence of benzaldehyde. Several4-acetyl-2,5-substituted A -1,3,4-oxadiazolines were reported to beformed by the reaction of acetic anhydride with an acyl hydrazone.

These references do not describe or disclose fluorinecontaining cyano-A-1,3,4-oxadiazolines or the process for the preparation thereof.

SUMMARY OF THE INVENTION This invention is directed to a compound of thefor- "ice cyanogen azide and a nitrile selected from an alkyl, orhaloalkyl nitrile or a cyanogen halide. These compounds are useful assoil fungicides.

DESCRIPTION OF THE PREFERRED- EMBODIMENTS This invention is directed tothe 5,5-bis(fluoroalkyl)- substituted 4-cyano-A -1,3,4-oxadiazolines.

The fluoroalkyl substituents of the compounds of this invention containup to 6 carbon atoms such as: difluoromethyl, w-hydroperfluoroethyl,i.e., 1,1,2,2-tetrafluoroethyl, w-hydroperfluoropropyl,w-hydroperfluorobutyl, whydroperfluoropentyl, w-hydroperfluorohexyl,trifluoromethyl, chlorodifluoromethyl, w-chloroperfluoroethyl,pentafluoroethyl, w-chloroperfluoropropyl, heptafluoropropyl,w-ChlOlOPCIflllOIOblltYl, nonafluorobutyl, w-chlO- roperfluoropentyl,undecafluoropentyl, w-chloroperfluorohexyl and tridecafluorohexyl. Thecompounds containing fluoroalkyl groups of up to 4 carbons arepreferred.

The substituents in the 5 positions of the compounds of this inventioncan be perfluoroalkylidene groups. Perfluoroalkylene substituents suchas: hexafluoropropylidene (CH CF CF octafluorobutylidene anddecafluoropentylident (CF CF C F CF CF are included within the scope ofthe invention with perfluoroalkylidene substituents containing 4 and 5carbons being preferred.

The term R in Formula I can be lower alkyl, lower haloalkyl or halogenand can contain up to 6 carbons such as: methyl, ethyl, n-propyl,isopropyl, n-butyl, 2-butyl, pentyl, hexyl, dichloromethyl,dibromomethyl, dii0do methyl, 2-chloroethyl, 2-bromoethyl,3-bromo-n-propyl, wiodopentyl, w-chlorohexyl and the like. The halogenof the haloalkyl group is fluorine, chlorine, bromine or iodine.Compounds with R having up to 4 carbons and chlorine are preferred. Rcan also be halogen such as: fluorine, chlorine, bromine or iodine.

The process of this invention can be described by the equation whereinR, X, m and n are as defined above. The process comprises heating at atemperature of 25-125 C., and preferably at a temperature of 40-75" C.,a mixture of cyanogen azide (II), a fluoroketone (III) and a nitrile(IV). The reaction can be conducted in a batch or flow system usually atatmospheric pressures. The process can be conducted at either reduced orsuperat-mospheric pressure.

It is convenient to conduct the process in the presence of excessnitrile or fluoroketone reactant or in the presence of nonreactivesolvents or diluents such as an ester such as ethyl acetate or ahalocarbon such as methylene chloride or chloroform. An excess of up tol00-fold of any reactant can be used, but an excess of the ketone and/ornitrile reactant is desirable for best results. The process reagent,especially if an excess of the cyanogen halide has been used asprecursor to cyanogen azide in preparing the latter. Occasionally aresidual amount of cyanogen halide (normally removed) may beinadvertently present in the cyanogen azide reagent. If an organicnitrile is added to a mixture containing cyanogen azide, a ketone andresidual cyanogen halide, the cyanogen halide will generally reactpreferentially. In this event, the organic nitrile will reactsecondarily or may serve merely as a less reactive medium.

The reactants used in the process are readily available or can be easilyprepared. For example, the fluoroketones III are well-known materialswhich have been described in Lovelace, Rausch and Pastelnek, AliphaticFluorine Compounds, Reinhold Publishing Corporation, New York, 1958, pp.190-192.

Cyanogen azide, described and claimed in my US. Pat. 3,410,658, isexplosive when free of solvent and should be handled with care. Alkylnitriles, haloalkyl' 5,5 -bis( difluorochloromethyl)-2-methyl-A -1,3,4-

oxadiazoline-4-carbonit1ile N2 (CIOF2)2CO NaGN CH ON (OlCFzhC-O NC-No-oH,,

Cyanogen azide (3.4 g., 0.05 mole) in acetonitrile (total solutionvolume, 14.2 ml.) was added to 1,3-dichlorotetrafluoroacetone, and themixture was stirred and heated at 48-52 C. for 21.5 hours during whichtime nitrogen (ca. 0.04 mole) was liberated. Volatile materials wereremoved on a rotary evaporator (0.3 mm./ 35 C.) to give a brown oil(9.50 g., 68%). The oil was distilled in a short path still at 035p (pottemp. 61-100 C.) to give a straw colored oil (4.42 g.) of5,5-bis(difiuorochloromethyl) 2 methyl-A -1,3,4oxadiazoline-4-carbonitrile.

Analysis.Calcd. for C H N F Cl O (percent): C, 25.74; H, 1.08; N, 15.01;F, 27.14; Cl, 25.33. Found (percent): C, 25.64; H, 1.08; N, 14.51; F,26.78; Cl, 25.77, 26.77.

The H n.m.r. spectrum (undiluted sample) showed a single absorption peak(17.79); and the F n.m.r. spectrum showed a single fluorine resonance at220 cps. (from symtetrachlorodifluoroethane as external standard, 56.1mc.). 1

Infrared absorption occurred at 3.41,u.'(saturated C-H), 4.47; (GEN),and 4.94 1. (C N).

In a similar preparation the crude product, obtained in 76% yield, wasfractionated in a spinning-band column to give a colorless oil (B.P.38-40" C./0.5 mm; 11 1.4170). This fraction was shown by gaschromatography to be better than 99% pure.

Mass spectroscopic analysis of the product gave a fragment ion of CH CO+(43 m/ e); parent ion, 279; isotopes 280-283. Calcd. M.W. is 280.

7 EXAMPLE 2 ,5 -bis (trifluoromethyl) -2-methyl-A 1 ,3,4-

oxadiazoline 4-carbonitrile Cyanogen azide'(0.09 mole) in acetonitrile(30 ml., totalsolution'volume) was added to a hydrogen fluorideresistantbomb under nitrogen. The bomb was closed, cooled, and evacuated; andhexafluoroacetone (28.5 g.)

was added by gas transfer. The reaction mixture was'agitated' and heatedat 50 C./60100 p.s.i. for 8 hours, and at 60 C./ 130-190 p.s.i. for 7hours more. The bomb Was vented, and the liquid fraction removed. Liquidfractions from two identical runs were combined and the volatilesremoved on a rotary evaporator (0.2 mm./ 30 C.). A brown oil (39 g.,87.5%) was obtained which was distilled in a short path still to give acolorless product (19.56 g., 44%). A portion from a collection of suchproducts from several runs was fractionated through a 17" x 10 mm.spinning-band column to give a refined sample (B.P. 55-57 C./16 mm, 111.3526) of 5,5-bis (trifluoromethyl)-2-methyl-A -1,3,4-oxadiazoline 4carbonitrile. Vapor phase chromatography indicatedthis sample to be93-98% pure, andpreparat'ive' scale gas chromatography of a portion ofit gave analytically pure material (B.P. 68 C./77 mm, m 1.3550).

Analysis-Called. for C H F N 0 (percent): C, 29.16; H, 1.22; F, 46.13;N, 17.01; M.W., 247. Found (percent): C, 29.35; H, 1.61; F, 45.56,46.77, 45.55; N, 17.31, 17.42; M.W., 247 (mass spec.)

The H nm.r. spectrum (undiluted sample using tetramethylsilane asinternal standard) showed a single proton resonance (T7.8O);-and the Fn.m.r. spectrum showed a single fluorine resonance at709 cps. froms-tetrachlorodifiuoroethane, (56.4 mc.).

The pure compound absorbed in the infrared region at 3.4/1. (saturatedC-H), 4.6a (GEN), 5.9a (C==N), and in the 8 region (C-E). J

Mass spectroscopic analysis of the products gave a fragment ion of CHCO+ (43 m/e).

EXAMPLE 3 5-(4H-octafluorobutyl)-5-(ZH-tetrafluoroethyl)-2-methyl- A-1,3,4-oxadiazoline-4-carbonitrile Cyanogen azide (10.2 g., 0.15 mole)in'acetonitrile (62.5 cc. total solution volume was added to 1H, 7H-dodecafluoro-3-heptanone (50 g., 0.15 mole), and the mixture was heatedand stirred at 47-62? C. 01122 hours during which time nitrogen (ca 0.15mole) was liberated. The reaction mixture was filtered, and the filtratewas evaporated to dryness on a rotary evaporator (1 mm, 30 C.) to give aviscous liquid residue (46.7 g.). The residue was slurried. withmethylene chloride ml.) and filtered again. The methylene chloridefiltrate'was evaporated to dryness on a rotary evaporatorto givearesidual mobile light brown oil (28 g., 46%). This brown oil wasdistilled in a short path still to give 5-(4H-octafluorobutyD-S-(ZH-tetrafluoroethyl) 2-methyl-A' -l,3,4'-oxadiazoline-4-carhonitrile as a colorlessoil (20.8 g., 37%). An aliquot'(18 g.) of thecolorless oil was fractionate'd in a 6" Vig reux columntogive a pure product, RP. 76" C./3/.L; 11 13680. The infrared spectra, ofthe brown residual oil .and the fractionated product were identical. i

AnalysisL-Calcid. for C H F N 0 (percent): C, 29.21; H, 1.23; N, 10.22;F, 55.45; M.W., 411.2. Found (percent): C, 28.82, 29.13; H,,.1.38,,1.37;.N, 10.65, 10.63; F, 55.46; M.W., 411, (mass spec), I

Infrared spectrumz 3.33;. (saturated (C-H), 4.46;]. (CEN), 5.91 1.((FN), 8-9; (C.F). H n.m,r. spectrum (undiluted sample,tetramethylsilane' as internal standard).

5 EXAMPLE 4 5,S-bis(chlorodifluoromethyD-Z-(,B-chloroethyD-A1,3,4-oxadiazoline-4-carbonitrile ll ClCF2CCF2Cl NaCN ClCHzCHzCH(ClCF2)2C-O Cyanogen azide (13.6 g., 0.2 mole) dissolved in 1,3-dichlorotetrafluoroacetone (total volume 122 ml.) was added tofi-chloropropionitrile (54 g., 0.6 mole), and the mixture was stirredand heated at 4049 C. for 3 days during which time the nitrogen (-0.15mole) was liberated. The reaction mixture was concentrated on a rotaryevaporator (1 mm./25 C.) and the concentrate' filtered. The filtrate wasdistilled in a molecular still to separate unreactedB-chloropropionitrile and essentially pure product (9.1 g.). The productwas fractionated through a 6" Vigreux column to give analytically pure5,5-bis(chlorodifluoromethyD-Z-(B-chloroethyl) A 1,3,4-oxadiazoline-4-carbonitrile (B.P. 78 C./3,U.; n 1.4436.

Analysis-Calm. for C H F N CI O (percent): C, 25.59; H, 1.23; N, 12.79;F, 23.14; M.W., 328.5. Found (percent): C, 25.83, 25.88; H, 1.49, 1.37;N, 12.79, 12.94; F, 23.40; M.W., 328 (mass spec.)

Infrared spectrum: 3.38; (C-H), 4.45, (GEN), 5.95 (C=N). H n.m.r.spectrum: (undiluted sample, tetramethylsilane as internal standard).

Two distorted triplets (A X pattern) centered at 1- 6.20 and 6.09.

F n.m.r. spectrum: (neat sample, fluorotrichloromethane as externalstandard).

Single peak, 635 ppm, 56.4 mc. Mass spectrum: contained a 91 m./e. ionCICH CH CO EXAMPLE 5,5-bis(chlorodifiuoromethyl)-2-chloro-A -1,3,4-

A solution of cyanogen azide (13.6 g., 0.2 mole) in1,3-dichlorotetrafiuoroacetone (total solution volume 127 ml.)containing cyanogen chloride was added to a 200 ml. hydrogen fluorideresistant bomb and evacuated to -400 mm. pressure. Trifiuoroacetonitrile(37 g., 0.44 mole) was added as a gas. The mixture was heated andagitated for 8 hours at 5052 C. and then for 8.5 hours at 5 8-60" C. Thebomb was cooled to room temperature and volatile materials were vented.The liquid fraction was filtered and the filtrate concentrated in arotary evaporator (285 mm./25 C.) to give a brown mobile oil (18.25 g.,30%). This oil was distilled in a short path still at a pot temperatureat 25-115 C. and a pressure of 100-102 mm. to give a colorless oil (7.35g., 12%). Products from this and a similar run were combined, and analiquot of the whole was purified by vapor phase chromatography [2' x A"OD. column packed with 25% fiuorosilicon (FS 1265) on firebrick; columntemperature 125 C.; helium flow rate 300 mL/minute]. The productcollected at 5.25 minutes (2.35 g; B.P. 52 C./4 mm.; n 1.4260) analyzedcorrectly for 5,5-bis(chlorodifiuoromethyl)-2-chloro A 1,3,4oxadiazoline 4 carbonitrile.

Analysis.-Calcd. for C Cl F N O (percent): C, 19.99; Cl, 35.39; F,25.29; N, 13.98; M.W., 300. Found (percent): C, 20.37, 20.17; Cl. 35.17;F, 25.22; N, 14.03 14.05; M.W., 299, 301 (mass spec.)

Infrared spectrum: 4.43,u (C=N), 6.08 (C N), 8-9 t (CF and/ or CO). Fn.m.r. spectrum: (undiluted sample, fluorotrichloromethane as externalstandard). Single peak,

6 3588 cps. 56.4 mc. Mass spectrum: contained a 65 m./c. ion ClCO+).

The N-cyanooxadiazolines of this invention are useful as soilfungicides. For example, the compounds which are produced in Examples 1and 2 have been found to inhibit the growth of Rhizoctonia and Pythium.

Rhizoctonia spp. is a common soil fungi. The species Rhizoctonia solani,for example, attacks many valuable plants including: (1) Field cropssuch as alfalfa, cotton, peanuts, sugar beets, sugar cane, and soybeans;(2) Ornamentals and house plants such as aster, begonia, camation andthe like; (3) Cereals and grasses such as barley, bent grass, rye, oats,and wheat; and (4) Truck crops such as beans, beets, cucumbers,eggplant, lettuce, onions, potatoes, and tomatoes.

In general, plant protectant compositions containing compounds of thisinvention contain one or more surface active agents. Surfactants can bepresent in compositions in the range of 0.1 to 20 percent with 02-10% byweight preferred. Active surfactants useful in the plant protectantcompositions are disclosed in US. Patents 2,412,510; 2,426,417 and2,655,447. The compounds can be applied to the soil, before or afterplanting, or application can be made to growing plants. The rate ofapplication will vary and will generally be in excess of the amountnecessary to control the fungi. Generally, the compounds of thisinvention are applied to soils in amounts ranging from 0.05 pounds peracre or less to 20 pounds per acre. More can of course be used.

The following example illustrates the method of producing plants fromplant fungi such as Rhizoctonia.

EXAMPLE A The product of Example 1 was dissolved in acetone and appliedat a rate equivalent to 1 pound per acre to soil inoculated withRhizoctonia solani. Compounds of Example 1 gave about control, based onthe germination of the seeds.

The procedure of Example A was repeated using the product of Example 2with soil inoculated with Pythium. About 100% control was achieved.

The cyano compounds of this invention are hydrolyzed in excellent yieldto the corresponding new amides by treatment of the cyano compounds withconcentrated hydrochloric acid at room temperature or with hydrogenperoxide at lower temperatures. For example, when the product of Example1 was hydrolyzed, there was obtained 5,5bis(difiuorochloromethyl)-2-methyl-A -1,3,4- oxadiazoline-4-carboxamide,M.P. 141.4 C. When the product of Example 2 was hydrolyzed there wasobtained 5 ,5 -bis trifluoromethyl) -2-methyl-A 1,3,4-oxadiazoline-4-carboxamide, M.P. 121.8123.2 C.

The foregoing detailed description has been given for clarity ofunderstanding only and no unnecessary limitations are to be understoodtherefrom.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as folows:

1. A compound of the formula wherein (a) R is halogen, lower alkyl orlower haloalkyl where the halogen is fluorine, chlorine, bromine oriodine;

(b) the Xs, singly, can be the same or different and are hydrogen,chlorine or fluorine;

(c) the Xs, taken together, are CF and (d) n and m are integers of l6,inclusive; and when the Xs are taken together the sum of n and m is aninteger of 2-4, inclusive.

2. The compound of claim 1 wherein the Xs are Cl, n and m each is 1 andR is CH said compound being 5,5-bis(difluorochloromethyl)-2-methyl-A-1,3,4 oxadiazoline-4-carbonitrile.

3. The compound of claim 1 wherein the Xs are fluorine, n and m each isl and R is CH said compound being 5,5-bis(trifiuormethyl 2 methyl-A-1,3,4-oxadiazoline-4-carbonitrile.

4. The compound of claim 1 where the Xs are hydrogen, n and each m is 4and R is CH said compound being 5-(4H-octafiuorobutyl) 5(2H-tetrafluoroethyl)-2- methyl-A -1,3,4-oXadiazoline-4-carbonitrile.

5. The compound of claim 1 where the Xs are chlorine, n and m each is 1and R is fl-chloroethyl; said compound being5,5-bis(chlorodifluoromethyl 2 (fl-chloroethyl-A1,3,4-oxadiazoline-4-carbonitri1e.

6. The compound of claim 1 where the Xs are chlorine, n and In each is 1and R is chlorine; said compound being5,5-bis(chlorodifiuoromethyl)-2Pch1oro A 1,3,4-oxadiazolineA-carbonitrile.

7. A process for preparing a compound of claim 1 comprising heating at atemperature of -125 C. a mixture of cyanogen azide, a fiuoroketone ofthe formula F2)n- 2)mX and a nitrile of the formula RCN wherein X, R, nand m are as defined in claim 1.

8. The process of claim 7, wherein the reaction is conducted at 75 C.

9. The process of claim 7, comprising reacting a mixture of cyanogenazide, 1,3-dichlorotetrafluoroacetone and acetonitrile at a temperatureof 25l25 C.

10. The process of claim 7, comprising reacting a mixture of cyanogenazide, hexafluoroacetone and acetonitrile at a temperature of 25-125 C.

References Cited ALTON D. ROLLIN'S, Primary Examiner US. Cl. X.R.

